rs519704

Variant names:

• chr2-31580233-G-A
• rs519704
• NM_000348.4:c.281+387C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-31580233-G-A
• chr2-31580233-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000348.4(SRD5A2):​c.281+387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,214 control chromosomes in the GnomAD database, including 1,081 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1081 hom., cov: 33)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 3 publications found

Genes affected

SRD5A2 (HGNC:11285): (steroid 5 alpha-reductase 2) This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH). [provided by RefSeq, Jul 2008]

SRD5A2 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	NM_000348.4	MANE Select	c.281+387C>T		intron	N/A	NP_000339.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.281+387C>T		intron	N/A	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.281+387C>T		intron	N/A	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.281+387C>T		intron	N/A	ENSP00000552702.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17554 AN: 152096 Hom.: 1079 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17570 AN: 152214 Hom.: 1081 Cov.: 33 AF XY: 0.115 AC XY: 8528 AN XY: 74408

African (AFR) AF: 0.138 AC: 5728 AN: 41530

American (AMR) AF: 0.0889 AC: 1360 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3470

East Asian (EAS) AF: 0.103 AC: 533 AN: 5158

South Asian (SAS) AF: 0.0981 AC: 473 AN: 4820

European-Finnish (FIN) AF: 0.0976 AC: 1035 AN: 10604

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7106 AN: 68006

Other (OTH) AF: 0.127 AC: 269 AN: 2114

Alfa AF: 0.0418 Hom.: 34

Bravo AF: 0.115

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.82
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs519704; hg19: chr2-31805303;